ATP-triggered anticancer drug delivery

被引:616
作者
Mo, Ran [1 ,2 ,3 ,4 ]
Jiang, Tianyue [1 ,2 ,3 ,4 ]
DiSanto, Rocco [1 ,2 ]
Tai, Wanyi [1 ,2 ,3 ]
Gu, Zhen [1 ,2 ,3 ]
机构
[1] Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27695 USA
[2] N Carolina State Univ, Raleigh, NC 27695 USA
[3] Univ N Carolina, Eshelman Sch Pharm, Mol Pharmaceut Div, Chapel Hill, NC 27599 USA
[4] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
基金
美国国家科学基金会;
关键词
CANCER-THERAPY; INTRACELLULAR ATP; LOADED LIPOSOMES; INSULIN DELIVERY; ANNEXIN-V; RELEASE; APOPTOSIS; DNA; THERAPEUTICS; MECHANISMS;
D O I
10.1038/ncomms4364
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 mu M in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.
引用
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页数:10
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